Pyrrolo[2,1-b] [3]benzazepines useful for producing a skeletal muscle relaxing or tranquilizing effect

Abstract

11-Aminopropylidene-Pyrrolo[2,1-b] [3]benzazepines are disclosed to have pharmaceutical utility as skeletal muscle relaxants and tranquilizers. They are prepared by a Grignard reaction on pyrrolo[2,1-b] [3]benzazapin-11-ones followed by dehydration, or by a Wittig reaction on the same ketones.

What is claimed is: 
     
       1. A compound of structural formula: ##STR27## or pharmaceutically acceptable salt thereof, wherein the dotted line represents saturation or unsaturation; X and Y are independently selected from (1) hydrogen   (2) halo,   (3) formyl,   (4) C 2-6  -alkanoyl,   (5) C 1-5  -alkyl,   (6) (C 1-5  -alkoxy)carbonyl,   (7) hydroxy-C 1-3  -alkyl,   (8) trifluoromethyl   (9) C 1-3  -alkoxy   (10) cyano,   (11) trifluoromethylthio,   (12) C 1-3  -alkylthio,   (13) C 1-3  -alkylsulfonyl,   (14) trifluoromethylsulfonyl,   (15) C 1-3  -alkylsulfinyl,   (16) trifluoromethylsulfinyl,   (17) amino,   (18) C 2-6  -alkanoylamino,   (19) C 1-3  -alkylamino,   (20) di(C 1-3  alkyl)amino,   (21) hydroxy,   (22) N-C 1-3  -alkylcarbamoyl,   (23) N,N-di(C 1-3  alkyl)carbamoyl,   (24) nitro,   (25) di(C 1-3  alkyl)sulfamoyl,   (26) C 1-3  alkoxycarbonylamino, and   (27) N-C 1-3  alkylcarbamoyloxy; and R 1  and R 2  are independently selected from   (1) hydrogen,   (2) C 1-3  -alkyl,   (3) C 2-5  alkenyl, and   (4) C 3-6  -cycloalkyl, or R 1  and R 2  joined together form with the nitrogen to which they are attached 1-piperidyl, 1-pyrrolidyl, or 4-morpholinyl.     
     
     
       2. The compound of claim 1 wherein one of X and Y is hydrogen, and the other is hydrogen, cyano, formyl, C 2-6  alkanoyl, or chloro. 
     
     
       3. The compound of claim 2 wherein X is hydrogen, Y is 9-chloro and R 1  and R 2  are methyl. 
     
     
       4. The compound of claim 3 which is (E)-9-chloro-11-(3-dimethylaminopropylidene)-6,11-dihydro-5H-pyrrolo[2,1-b][3]benzazepine or a pharmaceutically acceptable salt thereof. 
     
     
       5. The compound of claim 3 which is (E)-9-chloro-11-(3-dimethylaminopropylidene)-11H-pyrrolo[2,1-b][3]benzazepine or a pharmaceutically acceptable salt thereof. 
     
     
       6. A compound of structural formula: ##STR28## wherein the dotted line represents unsaturation or saturation; X.sub.α and Y.sub.α are independently selected from (1) hydrogen,   (2) halo,   (3) C 2-6  -alkanoyl,   (4) C 1-5  -alkyl,   (5) (C 1-5  -alkoxy)carbonyl,   (6) hydroxy-C 1-3  -alkyl,   (7) trifluoromethyl   (8) C 1-3  -alkoxy,   (9) cyano,   (10) trifluoromethylthio,   (11) C 1-3  -alkylthio,   (12) C 1-3  -alkylsulfonyl,   (13) trifluoromethylsulfonyl,   (14) C 1-3  -alkylsulfinyl,   (15) trifluoromethylsulfinyl,   (16) amino,   (17) C 2-6  -alkanoylamino,   (18) C 1-3  -alkylamino,   (19) di(C 1-3  -alkyl)amino,   (20) hydroxy,   (21) N-C 1-3  -alkylcarbamoyl,   (22) N,N-di(C 1-3  -alkyl)carbamoyl,   (23) nitro,   (24) di(C 1-3  -alkyl)sulfamoyl,   (25) C 1-3  -alkoxycarbonylamino, and   (26) N-C 1-3  -alkylcarbamoyloxy; and R.sub.α 1  and R.sub.α 2  are independently selected from     (1) C 1-3  -alkyl,   (2) C 2-5  -alkenyl, and   (3) C 3-6  -cycloalkyl, or R.sub.α 1  and R.sub.α 2  together represent 1-piperidyl, 1-pyrrolidyl or 4-morpholinyl.     
     
     
       7. The compound of claim 6 wherein one of X.sub.α and Y.sub.α is hydrogen, and the other is hydrogen, cyano, C 2-6  alkanoyl or chloro. 
     
     
       8. The compound of claim 6 wherein X.sub.α is hydrogen, Y.sub.α is 9-chloro, and R.sub.α 1  and R.sub.α 2  are methyl. 
     
     
       9. A pharmaceutical composition for producing a skeletal muscle relaxing or tranquilizing effect comprising a pharmaceutical carrier and an effective amount of a compound of formula: ##STR29## or pharmaceutically acceptable salt thereof wherein the dotted line represents saturation or unsaturation; X and Y are independently selected from (1) hydrogen   (2) halo,   (3) formyl,   (4) C 2-6  -alkanoyl,   (5) C 1-5  -alkyl,   (6) (C 1-5  -alkoxy)carbonyl,   (7) hydroxy-C 1-3  alkyl,   (8) trifluoromethyl   (9) C 1-3  -alkoxy,   (10) cyano,   (11) trifluoromethylthio,   (12) C 1-3  -alkylthio,   (13) C 1-3  -alkylsulfonyl,   (14) trifluoromethylsulfonyl,   (15) C 1-3  -alkylsulfinyl,   (16) trifluoromethylsulfinyl,   (17) amino,   (18) C 2-6  -alkanoylamino,   (19) C 1-3  -alkylamino,   (20) di(C 1-3  -alkyl)amino,   (21) hydroxy,   (22) N-C 1-3  -alkylcarbamoyl,   (23) N,N-di(C 1-3  -alkyl)carbamoyl,   (24) nitro,   (25) di(C 1-3  -alkyl)sulfamoyl,   (26) C 1-3  -alkoxycarbonylamino, and   (27) N-C 1-3  -alkylcarbamoyloxy; and R 1  and R 2  are independently selected from     (1) hydrogen,   (2) C 1-3  -alkyl,   (3) C 2-5  -alkenyl, and   (4) C 3-6  -cycloalkyl, or R 1  and R 2  joined together form with the nitrogen to which they are attached 1-piperidyl, 1-pyrrolidyl, or 4-morpholinyl.     
     
     
       10. The pharmaceutical composition of claim 9, wherein X is hydrogen, Y is 9-chloro and R 1  and R 2  are methyl. 
     
     
       11. The composition of claim 10 wherein the compound is (E)-9-chloro-11-(3-dimethylaminopropylidene)-6,11-dihydro-5H-pyrrolo[2,1-b][3]-benzazepine or a pharmaceutically acceptable salt thereof. 
     
     
       12. The composition of claim 10 wherein the compound is (E)-9-chloro-11-(3-dimethylaminopropylidene)-11H-pyrrolo[2,1-b][3]benzazepine or pharmaceutically acceptable salt thereof. 
     
     
       13. A method of producing a skeletal muscle relaxant or tranquilizing effect in a patient in need of such treatment comprising the administration of an effective amount of a compound of formula: ##STR30## or pharmaceutically acceptable salt thereof, wherein the dotted line represents saturation or unsaturation; X and Y are independently selected from (1) hydrogen   (2) halo,   (3) formyl,   (4) C 2-6  -alkanoyl,   (5) C 1-5  -alkyl,   (6) (C 1-5  -alkoxy)carbonyl,   (7) hydroxy-C 1-3  -alkyl,   (8) trifluoromethyl   (9) C 1-3  -alkoxy   (10) cyano,   (11) trifluoromethylthio,   (12) C 1-3  -alkylthio,   (13) C 1-3  -alkylsulfonyl,   (14) trifluoromethylsulfonyl,   (15) C 1-3  -alkylsulfinyl,   (16) trifluoromethylsulfinyl,   (17) amino,   (18) C 2-6  -alkanoylamino,   (19) C 1-3  -alkylamino,   (20) di(C 1-3  -alkyl)amino,   (21) hydroxy,   (22) N-C 1-3  -alkylcarbamoyl,   (23) N,N-di(C 1-3  -alkyl)carbamoyl,   (24) nitro,   (25) di(C 1-3  -alkyl)sulfamoyl,   (26) C 1-3  -alkoxycarbonylamino, and   (27) N-C 1-3  -alkylcarbamoyloxy; and R 1  and R 2  are independently selected from     (1) hydrogen,   (2) C 1-3  -alkyl,   (3) C 2-5  -alkenyl, and   (4) C 3-6  -cycloalkyl, or R 1  and R 2  joined together form with the nitrogen to which they are attached 1-piperidyl, 1-pyrrolidyl, or 4-morpholinyl.     
     
     
       14. The method of claim 13 wherein X is hydrogen, Y is 9-chloro and R 1  and R 2  are methyl. 
     
     
       15. The method of claim 14 wherein the compound is (E)-9-chloro-11-(3-dimethylaminopropylidene)-6,11-dihydro-5H-pyrrolo[2,1-b][3]benzazepine or a pharmaceutically acceptable salt thereof. 
     
     
       16. The method of claim 14 wherein the compound is (E)-9-chloro-11-(3-dimethylaminopropylidene)-11H-pyrrolo[2,1-b][3]benzazepine or pharmaceutically acceptable salt thereof.